Irritable bowl syndrome is a chronic disorder of the intestines causing bloating, abdominal pain, constipation and/or diarrhoea. The symptoms of IBS have not been explained by anatomical or metabolic abnormalities. Rather, IBS is considered to be a biopsychosocial disorder resulting from a combination of three interacting mechanisms, i.e. altered bowl motility, increased visceral sensitivity, and psychosocial factors [Gastroenterol., 120, 652-668, 2001].
Irritable bowl disease is a common disease mainly effecting women and with an estimated prevalence in Europe and North America of 10-15%. The disease is, however, not well recognised and only a fraction of those subjects affected by the disease is actually formally diagnosed. The prevalence of patients diagnosed with IBS in eight European countries is only 2.8% in average [Aliment. Pharmacol. Ther., 24, 183-205, 2006].
Irritable bowl syndrome is normally divided into three subgroups defined by the predominant bowl habit, i.e. constipation-predominant (c-IBS), diarrhoea-predominant (d-IBS) and IBS with alternating symptoms of both constipation and diarrhoea (a-IBS).
Irritable bowl syndrome is being treated with various therapeutic agents including antispasmodics, laxatives, anti-diarrhoea agents, tri-cyclic antidepressants and 5-HT3 antagonists. Odansetron is a 5-HT3 antagonist, and the compound has in clinical trials been shown to improve stool consistency, bowel frequency and reduce the number of pain episodes. Alosetron, which is also a 5-HT3 antagonist, has been shown to improve abdominal pain or discomfort and faecal urgency [Aliment. Pharmacol. Ther., 24, 183-205, 2006]. Alosetron is licensed by the FDA for the treatment of women with severe diarrhoea-predominant IBS.
The compound 4-[2-(4-methylphenylsulfanyl)phenyl]piperidine was first disclosed in the international patent application published as WO 2003/029232 wherein the compound was shown to be a serotonin transport inhibitor. Later, in the international patent application published as WO 2007/144006 crystalline salts of said compound was disclosed together with a more extensive pharmacological profile including 5-HT3 antagonism.